A large Stanford study has linked estrogen only menopausal hormone therapy with lower chances of Alzheimer’s related brain changes and dementia in women. The findings, published Aug. 12 in Neurology, add pathological evidence to a controversial research area while stopping short of changing current clinical recommendations.

Researchers analyzed postmortem data from 21,462 participants. They compared 258 women who reported using estrogen only MHT with approximately 2,701 women who reported no MHT use.

The researchers examined participants’ brains for signs of Alzheimer’s disease, including amyloid plaques, neurofibrillary tangles and amyloid plaque density. Plaques and tangles are two hallmark brain changes associated with the common form of dementia.

Women who used estrogen only therapy had a 35% lower chance of Alzheimer’s pathology and 39% lower odds of dementia over a lifetime. Most of the women who received this form of therapy had likely undergone hysterectomies.

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Among some participants who were still living, estrogen only users also performed better on memory testing. The study found that they were better able to function independently, while biomarkers in blood and cerebrospinal fluid supported the findings.

The researchers noted that recent research indicates menopausal hormone therapy may provide greater benefits when treatment begins during or shortly after menopause. Because women in this study were generally older when they started treatment, the results may understate the potential benefits of beginning therapy earlier.

The findings appear to contradict previous studies that connected menopausal hormone therapy with an increased risk of dementia. Alzheimer’s disease is the leading cause of dementia among older adults, and women account for about two thirds of diagnoses.

Coauthor Jennifer Bruno, PhD, an instructor in psychiatry and behavioral sciences, told Fox News Digital that estrogen has shown neuroprotective effects in animal models. She said estrogen plays a role in processes involving amyloid and tau, which are both hallmarks of Alzheimer’s disease.

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Bruno also said estrogen supports synaptic plasticity, reduces neuroinflammation and supports the integrity of the blood brain barrier. Therefore, she said the finding of less Alzheimer’s disease pathology among estrogen only users was consistent with those mechanisms.

Memory can be affected by many different conditions, the researchers noted, which means clinical diagnoses can sometimes be unreliable. Bloodborne and cerebrospinal fluid biomarkers have advanced, but they do not reveal the amount and precise location of brain damage.

Senior author Hadi Hosseini, Ph.D., an associate professor of psychiatry and behavioral sciences at Stanford, said examining the brain allows researchers to identify where defining features associated with Alzheimer’s disease are located. It also allows them to determine how many of those features are present.

However, the study had limitations. Because it was observational, it could show an association but could not establish that hormone therapy reduced Alzheimer’s risk.

Hosseini said women who used hormone therapy may have differed from those who did not use it in ways the researchers could not fully measure. Those differences could have included baseline health status or engagement with health care.

The researchers adjusted for known confounders and accounted for which participants did and did not come to autopsy. Even so, Hosseini emphasized that observational data remain limited and that carefully designed clinical trials are needed to confirm the findings.

The results do not change current clinical recommendations, according to Hosseini. Instead, they highlight the need to determine whether menopausal hormone therapy has a protective cognitive effect through additional research.

Bruno characterized the pathological evidence as meaningful and the first of its kind within a genuinely controversial field. At the same time, she said the results are a signal for further study rather than a reason to begin or stop MHT for brain health.

The researchers called for prospective trials using biomarkers to follow women before, during and after menopause. Such studies could help researchers better understand the effects of MHT on brain health.

The National Institutes of Health funded the study. Its findings provide new evidence about an association between estrogen only therapy and Alzheimer’s pathology, but researchers cautioned that confirmation will require additional clinical research.